| 名稱(chēng) | Lenvatinib |
| 描述 | Lenvatinib (E7080) is a multi-target receptor tyrosine kinase inhibitor that inhibits VEGFR1-3, FGFR1-4, KIT, PDGFR, and RET, and has oral activity. Lenvatinib has the strongest inhibitory activity on VEGFR2 and VEGFR3 (IC50=4/5.2 nM). Lenvatinib has strong anti-tumor activity. |
| 細(xì)胞實(shí)驗(yàn) | HUVECs (1,000 cells in each well in serum-free medium containing 2% fetal bovine serum) and L6 rat skeletal muscle myoblasts (5,000 cells in each well in serum-free DMEM) are dispensed in a 96-well plate and incubated overnight. E7080 and either VEGF (20 ng/mL) or FGF-2 (20 ng/mL) containing 2% fetal bovine serum and PDGFβ (40 ng/mL) are added to each well. Cells are incubated for 3 days and then the ratios of surviving cells are measured by WST-1 reagent. For proliferation assay, samples are duplicated and three separate experiments are done. (Only for Reference) |
| 激酶實(shí)驗(yàn) | In vitro kinase assay [1]: Tyrosine kinase assays are performed by HTRF (KDR, VEGFR1, FGFR1, c-Met, EGFR) and ELISA (PDGFRβ), using the recombinant kinase domains of receptors. In both assays, 4 μL of serial dilutions of E7080 are mixed in a 96-well round plate with 10 μL of enzyme, 16 μL of poly (GT) solution (250 ng) and 10 μL of ATP solution (1 μM ATP) (final concentration of DMSO is 0.1%). In wells for blanks, no enzyme is added. In control wells no test article is added. The kinase reaction is initiated by adding ATP solution to each well. After 30-minute incubation at 30°C, the reaction is stopped by adding 0.5 M EDTA (10 μL/well) to the reaction mixture in each well. Dilution buffer adequate to each kinase assay is added to the reaction mixture. In the HTRF assay, 50 μL of the reaction mixture is transferred to a 96-well 1/2 area black EIA/RIA plate, HTRF solution (50 μL/well) is added to the reaction mixture, and then kinase activity is determined by measurement of fluorescence with a time-resolved fluorescence detector at an excitation wavelength of 337 nm and an emission wavelengths of 620 and 665 nm. In the ELISA, 50 μL of the reaction mixture is incubated in avidin coated 96-well polystyrene plates at room temperature for 30 minutes. After washing with wash buffer, PY20-HRP solution (70 μL/well) is added and the reaction mixture is incubated at room temperature for 30 minutes. After washing with wash buffer, TMB reagent (100 μL/well) is added to each well. After several minutes (10–30 minutes), 1 M H3PO4 (100 μL/well) is added to each well. Kinase activity is determined by measurement of absorbance at 450 nm with a microplate reader. |
| 體外活性 | 方法：六種人腫瘤細(xì)胞 A375、DU145、DX3、KM12C、SK23 和 U2OS 用 Lenvatinib (1-100 μM) 處理 72 h，使用 MTT 檢測(cè)細(xì)胞活力。
結(jié)果：大多數(shù)細(xì)胞系中，Lenvatinib 僅在高濃度下抑制增殖 (IC50 為 23.6-44.17 μM)，而 KM12C 細(xì)胞系中的 IC50 為 9.54 μM。[1]
方法：人臍靜脈內(nèi)皮細(xì)胞 HUVECs 用 Lenvatinib (0.16-20 nM) 處理 1 h，隨后用 SCF 或 VEGF (20 ng/mL) 刺激 5 min，使用 Western Blot 方法檢測(cè)靶點(diǎn)蛋白表達(dá)水平。
結(jié)果：配體誘導(dǎo)的 KIT 和 KDR 的磷酸化均被 Lenvatinib 抑制。[2] |
| 體內(nèi)活性 | 方法：為檢測(cè)體內(nèi)抗腫瘤活性，將 Lenvatinib (30-100 mg/kg in 0.5% methylcellulose) 口服給藥給攜帶人小細(xì)胞肺癌腫瘤 H146 的 BALB/c nude 小鼠，每天兩次，持續(xù)二十一天。
結(jié)果：口服 Lenvatinib 以劑量依賴(lài)性方式抑制 H146 腫瘤的生長(zhǎng)，并在 100 mg/kg 時(shí)引起腫瘤消退。[2]
方法：為檢測(cè)體內(nèi)抗腫瘤活性，將 Lenvatinib (100 mg/kg) 口服給藥給攜帶人乳腺癌腫瘤 MDA-MB-231 的 nude 小鼠，每天一次，持續(xù)八周。
結(jié)果：Lenvatinib 在 MDA-MB-231 異種移植物模型中抑制向區(qū)域淋巴結(jié)和遠(yuǎn)處肺的轉(zhuǎn)移。Lenvatinib 降低了淋巴結(jié)中 MDA-MB-231 腫瘤的已建立轉(zhuǎn)移結(jié)節(jié)的血管生成和淋巴管生成。[3] |
| 存儲(chǔ)條件 | store at low temperature | Powder: -20°C for 3 years | Shipping with blue ice. |
| 溶解度 | DMSO : 15 mg/mL (35.14 mM), Sonication is recommended.(The compound is unstable in solution, please use soon.)
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 1.9 mg/mL (4.45 mM), Please add co-solvents sequentially, clarifying the solution as much as possible before adding the next one. Dissolve by heating and/or sonication if necessary. Working solution is recommended to be prepared and used immediately.
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| 關(guān)鍵字 | SCFR | PDGFR | CD117 | Platelet-derived growth factor receptor | Fibroblast growth factor receptor | 倫伐替尼 | RET | Lenvatinib | inhibit | c-Kit | E-7080 | VEGFR | E 7080 | FGFR | Inhibitor | Vascular endothelial growth factor receptor | 倫伐替尼 | 倫伐替尼 |
| 相關(guān)產(chǎn)品 | Imatinib | Amlexanox | Gilteritinib | Ribociclib | Formononetin | Axitinib | Ferulic Acid | Regorafenib | Pazopanib | Nintedanib | Sorafenib | Regorafenib monohydrate |
| 相關(guān)庫(kù) | 經(jīng)典已知活性庫(kù) | 抗癌活性化合物庫(kù) | 抗癌上市藥物庫(kù) | 已知活性化合物庫(kù) | EMA 上市藥物庫(kù) | 激酶抑制劑庫(kù) | FDA 上市藥物庫(kù) | 膜蛋白靶向化合物庫(kù) | FDA 上市激酶抑制劑庫(kù) | 藥物功能重定位化合物庫(kù) | 酪氨酸激酶分子庫(kù) | 抗癌臨床化合物庫(kù) |